ABSTRACT: With the premise that U.S. Veteran demographics reveal an aging population with significant mobility limitation and oxidative stress is tightly linked to both of these characteristics, a series of skeletal muscle/vascular studies are proposed. Specifically, in a series of recent studies our group has documented positive vascular consequences of antioxidant supplementation during exercise in older subjects that negatively impacted young people. Further provocative findings revealed that following exercise training the older subjects were now also negatively impacted by the antioxidant supplementation. These findings have implications for the understanding of the complex balance between the positive effects of exercise-based rehabilitation, exercise induced oxidative stress, aging, frailty, and subsequent mobility limitation. Therefore four specific aims are proposed that will address the following: 1) Is acute exercise-induced oxidative stress greater in muscle or blood with age? 2) Which response to muscular work generates oxidative stress with age? 3) What are the acute vascular consequences of oxidative stress with age? And 4) The role of oxidative stress in the exercise-induced vascular adaptations with age. The Central Hypothesis of this grant proposal is that oxidative stress is a key mechanism that can be manipulated to contribute to the benefits of exercise in aging humans.